Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0226463
Funder
Australian Research Council
Funding Amount
$160,000.00
Summary
Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructu ....Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructure necessary for research groups to further develop and maintain their international reputations, will build stronger research collaborations between partner institutions and will attract researchers from overseas.Read moreRead less
Transporting proteins to and within mitochondria. Mitochondria are found in all of our cells and are essential for life. They act like a nuclear power plant, providing the bulk of energy - but they can also kill the cell if the mitochondrial wall (membrane) is opened. Mitochondria contain about 1000 different proteins to function properly but almost all of them are made outside the compartment and must squeeze in through narrow membrane channels. This project will provide new insights into how p ....Transporting proteins to and within mitochondria. Mitochondria are found in all of our cells and are essential for life. They act like a nuclear power plant, providing the bulk of energy - but they can also kill the cell if the mitochondrial wall (membrane) is opened. Mitochondria contain about 1000 different proteins to function properly but almost all of them are made outside the compartment and must squeeze in through narrow membrane channels. This project will provide new insights into how proteins get into mitochondria and what factors help in this process. Besides providing new information about a process that is essential for life, the project will train students in molecular cellular biology techniques and will help foster strong international collaborations.Read moreRead less
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights ....Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights into endosomal trafficking at the molecular level. Outcomes from this work will place Australia at the forefront of international efforts to understand this essential biological process and will have important implications for future design of pharmaceuticals.Read moreRead less
Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrom ....Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrome c derivatives will be engineered in elongated or aggregated forms and their release studied (including interactions with putative release machinery components) following death-signal activation. The project will elucidate a central mechanism in the cell death process, highly significant in many biological contexts.Read moreRead less
A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research ....A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research standing.Read moreRead less
Defining the pathways for the import of proteins into mitochondria. This application deals with the targeting of preproteins from the cytosol to the mitochondria in mammalian cells. The aims are to identify and characterise mitochondrial targeting signals within preproteins lacking typical N-terminal signal sequences; to characterise the roles of the cytosolic molecular chaperones such as Hsp90 and Hsp70 in assisting the movement of preproteins to the mitochondrial surface; to determine the inte ....Defining the pathways for the import of proteins into mitochondria. This application deals with the targeting of preproteins from the cytosol to the mitochondria in mammalian cells. The aims are to identify and characterise mitochondrial targeting signals within preproteins lacking typical N-terminal signal sequences; to characterise the roles of the cytosolic molecular chaperones such as Hsp90 and Hsp70 in assisting the movement of preproteins to the mitochondrial surface; to determine the interactions of both preproteins and cytosolic factors with outer membrane components and; to analyse the roles of individual TOM receptors in import. The results obtained will facilitate our understanding of general protein import processes and those specific for mammals.Read moreRead less
A Cytosolic Complex for Targeting Mitochondrial Proteins. Mitochondria are essential for the viability of cells, and are the major source of cellular energy via oxidative phosphorylation. A loss of mitochondrial function with age contributes to the ageing process and therefore understanding the basic functions of this organelle is an important aim in biology. In mammalian cells this organelle comprises about 1500 different proteins, 99% of which need to be imported from outside the organelle. ....A Cytosolic Complex for Targeting Mitochondrial Proteins. Mitochondria are essential for the viability of cells, and are the major source of cellular energy via oxidative phosphorylation. A loss of mitochondrial function with age contributes to the ageing process and therefore understanding the basic functions of this organelle is an important aim in biology. In mammalian cells this organelle comprises about 1500 different proteins, 99% of which need to be imported from outside the organelle. We have found that this requires a large protein complex to target the preproteins to the organelle. This research is directed to determining the component parts of this complex and the roles each component plays in the targeting process and in mitochondrial reproduction.Read moreRead less
Molecular Basis for the Mitochondrial Stress Response. The biogenesis of mitochondria depends on the co-ordinated expression of mitochondrial and nuclear genomes. Little is known about the extent and how the expression of both cellular genomes is co-ordinated. We have discovered a novel biological process, the mitochondrial stress response, whereby the establishment of stress within the mitochondria results in the upregulation of a suite of genes in the nucleus encoding proteins which rescue m ....Molecular Basis for the Mitochondrial Stress Response. The biogenesis of mitochondria depends on the co-ordinated expression of mitochondrial and nuclear genomes. Little is known about the extent and how the expression of both cellular genomes is co-ordinated. We have discovered a novel biological process, the mitochondrial stress response, whereby the establishment of stress within the mitochondria results in the upregulation of a suite of genes in the nucleus encoding proteins which rescue mitochondria from damage caused by stress. This project is to determine how stress is sensed in the mitochondrion and communicated to the nucleus resulting in alterations in gene expression. The project also aims to define the physiological role of mitochondrial chaperones in protein folding in the organelle.Read moreRead less